Castro, who in 1985 was set to become a professional boxer but suffered a bicycle accident that left him injured so badly that doctors told him he'd never be able to fight as a professional, recuperated from the accident and turned professional, defying the doctor's predictions, in 1987.
He became world champion in 1994 by beating defending champion Reggie Johnson in Buenos Aires. After defeating Alex Ramos by a knockout in two to retain the belt, he travelled to Monterrey, Mexico, to defend against former WBO and WBA world champion John David Jackson of Philadelphia. What began merely as an undercard world title fight in a Pay Per View program featuring Felix Trinidad versus Oba Carr and Julio Cesar Chavez versus Tony Lopez, soon became a fight that is part of boxing's lore. Castro was trailing badly on all three scorecards, with one eye closed and the other one only halfway opened, bleeding and taking combination after combination against the ropes, when the referee went in to stop the fight. The referee began to raise his hands signaling the fight stoppage, but before he could get in between the fighters and make it official, Castro landed a right hand to Jackson's chin and Jackson hit the floor, and instead of stopping the fight in Jackson's favor, the referee found himself counting at Jackson. Jackson got up, but he suffered one more knockdown and Castro completed what could be said that was one of the unlikiest turnarounds ever in a boxing fight, retaining the title by a knockout in the ninth round.
At the press conference after the fight, Castro called his winning punch La mano de Dios, (The hand of God), which is the same nickname that was given to a goal scored by Diego Maradona during a win by Argentina's national soccer team at the 1986 World Cup. Therefore, that moment became known as boxing's version of The hand of God. The fight, and its ending, were talked about for months on many boxing magazines and books.
Castro defended his title twice more, including a rematch win over Johnson, and then he lost the title to Shinji Takejara by a decision in twelve. He split two 10 round decisions with Roberto Duran, winning the first in Argentina, but losing the rematch in Panama, and then he gave Jackson a rematch, this time winning by a decision in ten.
Castro, a good autograph signer, has lost two recent world championship fights: on December of 2000, he went to Germany and lost by a knockout in 10 to the WBC's cruiserweight champion of the world Juan Carlos Gomez, and on February of 2002, he went to Phoenix and challenged IBF world Cruiserweight champion Vasiliy Jirov, a Kasakstan native who lives in Phoenix, losing by a decision in twelve. Despite his failures in his latest attempts to become a world champion again, he has not announced a retirement.
Currently, he has a record of 117 wins, 8 losses and 3 draws, with 82 knockout wins, which ranks him among the most prolific knockout winners in boxing history according to the records of Ring Magazine.